Breast cancer metastasis suppressor 1 (BRMS1) is destabilized by the Cul3–SPOP E3 ubiquitin ligase complex

Breast cancer metastasis suppressor 1 (BRMS1) suppresses metastasis without affecting primary tumorigenesis. The regulatory mechanism of BRMS1 at the protein level has not been revealed until recently. Here, we found that cullin 3 (Cul3), a component of E3 ubiquitin ligase, is a new binding partner of BRMS1 and the interaction between BRMS1 and Cul3 is mediated by the SPOP adaptor protein. Intriguingly, BRMS1 turns out to be a potent substrate that is ubiquitinated by the Cul3–SPOP complex. Knockdown of SPOP increases the level of BRMS1 protein and represses the expression of BRMS1 repressive target genes such as OPN and uPA in breast cancer cells. These results suggest that the novel regulatory mechanism of BRMS1 by Cul3–SPOP complex is important for breast cancer progression.

► BRMS1 interacts with Cul3 and SPOP.
► The interaction of BRMS1 with Cul3 is mediated by SPOP.
► BRMS1 is ubiquitinated by Cul3–SPOP E3 ubiquitin ligase complex.
► Down-regulation of SPOP inhibits BRMS1 degradation in breast cancer cells.
► Down-regulation of SPOP represses the expression of the BRMS1 repressive target genes in breast cancer cells.